A multi-scale computational model of the effects of TMS on motor cortex

Abstract

The detailed biophysical mechanisms through which transcranial magnetic stimulation (TMS) activates cortical circuits are still not fully understood. Here we present a multi-scale computational model to describe and explain the activation of different pyramidal cell types in motor cortex due to TMS. Our model determines precise electric fields based on an individual head model derived from magnetic resonance imaging and calculates how these electric fields activate morphologically detailed models of different neuron types. We predict neural activation patterns for different coil orientations consistent with experimental findings. Beyond this, our model allows us to calculate activation thresholds for individual neurons and precise initiation sites of individual action potentials on the neurons' complex morphologies. Specifically, our model predicts that cortical layer 3 pyramidal neurons are generally easier to stimulate than layer 5 pyramidal neurons, thereby explaining the lower stimulation thresholds observed for I-waves compared to D-waves. It also shows differences in the regions of activated cortical layer 5 and layer 3 pyramidal cells depending on coil orientation. Finally, it predicts that under standard stimulation conditions, action potentials are mostly generated at the axon initial segment of cortical pyramidal cells, with a much less important activation site being the part of a layer 5 pyramidal cell axon where it crosses the boundary between grey matter and white matter. In conclusion, our computational model offers a detailed account of the mechanisms through which TMS activates different cortical pyramidal cell types, paving the way for more targeted application of TMS based on individual brain morphology in clinical and basic research settings. Keywords

Morphology controls how hippocampal CA1 pyramidal neuron responds to uniform electric fields: a biophysical modeling study

“…For our artificial model, APs are always initiated at the axon initial segment during uniform EF stimulation, and then somatic APs are elicited since this site is closest to initial segment. Such prediction is comparable to earlier modeling studies of L3/5 pyramidal neurons 49 . Further, it has been shown that the EF threshold for activating cells is tightly related to field-induced physiological responses 49 , 51 , including motor evoked potential, direct wave (D-wave) and indirect wave (I-wave).…”

“…One central issue for interpreting neuromodulatory effects of magnetic or electric field stimulation is which element of targeted cells is most likely to be activated 33 , 49 . The inhomogeneity of conductance densities throughout the cell endows different elements with distinct threshold of activation.…”

“…These two factors codetermine the shape of membrane polarization, thus the field threshold for triggering APs and the initiation site of AP. Especially the latter may be the axon initial segment 49 , the location of maximal gradient of induced EF 33 , or where axons bend as they enter the white matter 31 , 50 . For our artificial model, APs are always initiated at the axon initial segment during uniform EF stimulation, and then somatic APs are elicited since this site is closest to initial segment.…”

A Physical Perspective to the Inductive Function of Myelin—A Missing Piece of Neuroscience

“…In particular, stimulations will occur at the position of the first myelin sheath, which is at the interface of gray matter (soma) and white matter (myelinated axon) (P14 in Figure 14 ). The original statement in the previous study is quoted here (Seo et al, 2016 ):…”

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“…There are many recent computational studies that simulate electrical stimulation of multicompartment neuron models with realistic morphologies. Seo et al [3] modeled cortical pyramidal neurons with the activating function derived from an external TMS field, which was obtained based on an individual macroscopic head model. Goodwin & Butson [4] also modeled cortical neurons subject to an external TMS field.…”